The use of non-invasive intracranial pressure monitoring, including intracranial pressure pulse morphology in patients with COVID-19, could calculate possible components associated with the presence of neurological symptoms in these patients, in addition to being a tool with the potential to monitor the repercussion of MV at cerebral compliance patient patients. In addition, it is likely that patients with COVID-19 also have cerebral embolization more frequently than healthy patients, which is justified by transcranial doppler ultrasound assessment. The aim of the study is to monitor this brain pressure using a non-invasive method of monitoring, with a helmet-like system in place, for 1 hour for 7 consecutive days. There will be no associated invasive procedure of any kind. Monitoring will be done by the criteria themselves, no place where the patient and the mandatory volunteer. Another objective is to capture signs of microembolisms (small strokes that have not yet manifested) by performing a doppler ultrasound on the head with a helmet also for 1 hour, in a single evaluation.

The study population will include inpatients with COVID-19 infection. The control group will be in patients who do not have Covid-19. The control group will consist of people with similar characteristics and who have not recovered. Patients who meet the inclusion criteria incorporated into the monitoring with a non-invasive intracranial pressure device for 1 hour during hospitalization (Brain4Care® device approved by ANVISA), being monitored for up to seven days, in addition to monitoring for 1 hour with a transcranial doppler ultrasound helmet DWL® in a single assessment. There will be no invasive procedures or other equipment used without due knowledge by Organs competent bodies. It does not collect collection or retention of any biological material.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) is an infectious disease transmitted one person to another mainly from cough and sneeze aerosols as well as from contaminated surfaces. The most common respiratory symptoms are dry cough, fever, and dyspnea, but the Severe Respiratory Acute Syndrome (SARS) can be installed increasing disease´s mortality. In addition, neurological symptoms have been described according the increase of severity and age. Changes of intracranial pressure (ICP) can partially explain the Central Nervous System (CNS) impairment due to COVID-19. The ICP waveform can bring relevant information about intracranial compliance, and, nowadays, it can be measured by non-invasive technology. Clinically, non-invasive ICP waveform assessment would help to understand the repercussion of Invasive Mechanical Ventilation (IMV) on CNS in COVID-19 persons. AIMS: This study aims to evaluate the ICP waveform in intubated and non-intubated COVID-19 persons. Furthermore, the association between ICP and IMV parameters, level of sedation, heart rate variability, neurological symptoms, neuroimage, and final discharge will be investigated. . METHODS: At least 30 COVID-19 individuals will be included within 72h from admission and 14 days from symptoms onset. They will be divided into two groups: non-intubated (n=15) and intubated, paired with non-COVID-19 ones (non-intubated and intubated non-COVID-19 groups, respectively). The non-invasive ICP monitoring will be daily performed for 7 consecutive days. The Brain4Care's device and Analytic System will be used to assess the three pulse peaks (P1, 2 and 3) at the ICP waveform. The following variables will be investigated: P1 and P2 amplitude, P2/P1 ratio, time to peak and time percentage of P2 higher than P1. For statistics, all variables will be tested as to their normal or non-normal distribution through appropriate statical analyzes. For basic demographic and clinical variables, descriptive data analysis will be used. The repetitive measurement Anova will be used for ICP outcomes throughout the days. Pearson's or Spearman´s correlations will be applied according to data distribution.

Inclusion Criteria:

For COVID-19 group:

• Men and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated or non-intubated Time between admission and study inclusion ≤ 72h For intubated group time between IUC admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring ICF signed by the participant or his/her legal representative*

No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Subjects intubated or non-intubated For intubated group time between IUC admission and study inclusion ≤ 72h Time between admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤14 days No neurological acute disease

For Controls Group:

Men and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring • For intubated group: ICF signed by the participant or his/her legal representative* Intubated patients for others causes than COVID-19 or neurological diseases IUC admission and study inclusion ≤ 72h No symptoms of COVID-19 on the last 15 days

• For healthy group: No previous neurological disease No chronic disease as Diabetes Mellitus Type 2, Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, hypertension or Chronic Kidney Disease (CKD)

No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously.

IUC admission and study inclusion ≤ 72h No neurological diseases

Exclusion Criteria:

• It will be excluded those who asked to stop their participation, and those with problems in acquiring ICP data.

This is a multicenter longitudinal study of 4 centers in Brazil: Hospital of São Paulo (Federal University of São Paulo), Benemérita Portuguese Charity Association, São Paulo-SP, ESHO Hospital Services Company AS, São Paulo, SP and Federal University of São Carlos, São Carlos-SP, from June to December of 2020. This will follow Helsinki recommendations for human protocols. This study was approved by Federal University of São Paulo's Human Research Ethics Committee (process number 4,050,985). The patients who completed the inclusion criteria (table 1) will be invited to participate, and they will receive an Informed Consent Form (ICF).

At least 60 subjects will be included, and they will be equally divided into 4 groups.

There isn't defined a plan to make individual participant data (IPD) available to other researchers yet.

for research

for research